The specific aims of the experiments proposed in this application are as follows: 1. To determine the capacity of cornea cells to stimulate cell-mediated immunity and humoral immunity in vivo and in vitro; 2. To determine the kinds and distribution of the various histocompatibility antigens in the cornea; 3. To determine the types of leukocytes participating in cornea graft rejection; and 4. To determine the specific target site of action of antibody in modulating cornea graft rejection. Inbred strains of rats will be immunized with whole corneas and isolated corneal cells, and the immune response determined using the cell-mediated lympholysis assay and the enzyme linked immunoassay procedure. The specific tissue antigens of the cornea which elicit cellular and humoral immunity will be determined using immunohistochemical techniques such as the immunoperoxidase procedure in order to specifically localize these antigens. The exact identity of cornea cell antigens will be determined using specific antisera directed against RT1 histocompatibility and Ia antigens which have been defined in inbred strains of rats. The exact identity of the various cells which infiltrate and participate in cornea graft rejection will be determined using specific immunohistochemical methodology and specific antisera which identify subpopulations of leukocytes, including T lymphocytes and T lymphocyte subsets such as suppressor cells, helper cells, and cytotoxic cells. B lymphocytes, macrophage, and other cells of the inflammatory type will be identified using a combination of histochemical and immunological reagents. Blocking antibody pretreatment and anti-idiotypic autoimmunization permit cornea allografts to survive significantly beyond the expected survival time. The mechanism of action of antibody pretreatment and autoimmunization will be determined. The main scientific discipline involved in the proposed work is immunology. In humans, the cornea allograft reaction can be a serious and difficult to manage clinical problem. In order to better manage and deal with this problem, we must know the antigens and cells involved in this reaction so that we will be able to prevent or suppress this unwanted response.